Publications

The Pirbright Institute publication directory contains details of selected publications written by our researchers.

There were a total of 1875 results for your search.
Goldeck D, Perry D M, Hayes J W P, Johnson L P M, Young J E, Roychoudhury P, McLuskey E L, Moffat K, Bakker A Q, Kwakkenbos M J, Frossard J-P, Rowland R R R, Murtaugh M P, Graham S P (2019)

Establishment of systems to enable isolation of porcine monoclonal antibodies broadly neutralizing the porcine reproductive and respiratory syndrome virus

Frontiers in Immunology 10, 572

Abstract

The rapid evolution of porcine reproductive and respiratory syndrome viruses (PRRSV) poses a major challenge to effective disease control since available vaccines show variable efficacy against divergent strains. Knowledge of the antigenic targets of virus-neutralizing antibodies that confer protection against heterologous PRRSV strains would be a catalyst for the development of next-generation vaccines. Key to discovering these epitopes is the isolation of neutralizing monoclonal antibodies (mAbs) from immune pigs. To address this need, we sought to establish systems to enable the isolation of PRRSV neutralizing porcine mAbs. We experimentally produced a cohort of immune pigs by sequential challenge infection with four heterologous PRRSV strains spanning PRRSV-1 subtypes and PRRSV species. Whilst priming with PRRSV-1 subtype 1 did not confer full protection against a subsequent infection with a PRRSV-1 subtype 3 strain, animals were protected against a subsequent PRRSV-2 infection. The infection protocol resulted in high serum neutralizing antibody titers against PRRSV-1 Olot/91 and significant neutralization of heterologous PRRSV-1/-2 strains. Enriched memory B cells isolated at the termination of the study were genetically programmed by transduction with a retroviral vector expressing the Bcl-6 transcription factor and the anti-apoptotic Bcl-xL protein, a technology we demonstrated efficiently converts porcine memory B cells into proliferating antibody-secreting cells. Pools of transduced memory B cells were cultured and supernatants containing PRRSV-specific antibodies identified by flow cytometric staining of infected MARC-145 cells and in vitro neutralization of PRRSV-1. Collectively, these data suggest that this experimental system may be further exploited to produce a panel of PRRSV-specific mAbs, which will contribute both to our understanding of the antibody response to PRRSV and allow epitopes to be resolved that may ultimately guide the design of immunogens to induce cross-protective immunity.

Guzman E, Pujol M E, Ribeca P, Montoya M (2019)

Bovine derived in vitro cultures generate heterogeneous populations of antigen presenting cells

Frontiers in Immunology 10, 612

Abstract

Antigen presenting cells (APC) of the mononuclear phagocytic system include dendritic cells (DCs) and macrophages (Macs) which are essential mediators of innate and adaptive immune responses. Many of the biological functions attributed to these cell subsets have been elucidated using models that utilize in vitro-matured cells derived from common progenitors. However, it has recently been shown that monocyte culture systems generate heterogeneous populations of cells, DCs and Macs. In light of these findings, we analysed the most commonly used bovine in vitro-derived APC models and compared them to bona fide DCs and Macs. Here, we show that bovine monocyte-derived DCs and Macs can be differentiated on the basis of CD11c and MHC class II (MHCII) expression and that in vitro conditions generate a heterologous group of both DCs and Macs with defined and specific biological activities. In addition, skin-migrating macrophages present in the bovine afferent lymph were identified and phenotyped for the first time. RNA sequencing analyses showed that these monophagocytic cells have distinct transcriptomic profiles similar to those described in other species. These results have important implications for the interpretation of data obtained using in vitro systems. 

Mulumba-Mfumu L K, Saegerman C, Dixon L K, Madimba K C, Kazadi E, Mukalakata N T, Oura C A L, Chenais E, Masembe C, Stahl K, Thiry E, Penrith M L (2019)

African swine fever: update on Eastern, Central and Southern Africa

Transboundary and Emerging Diseases 66 (4), 1462-1480
Publisher’s version: https://doi.org/10.1111/tbed.13187

Abstract

Control of African swine fever (ASF) in countries in Eastern, Central and Southern Africa (ECSA) is particularly complex owing to the presence of all three known epidemiological cycles of maintenance of the virus, namely an ancient sylvatic cycle involving the natural hosts and vectors of the disease as well as domestic cycles with and without involvement of natural vectors. While the situation is well documented in some of the countries, for others very little information is available. In spite of the unfavourable ASF situation, the pig population in the sub-region has grown exponentially in recent decades and is likely to continue to grow in response to rapid urban growth resulting in increasing demand for animal protein by populations that are no longer engaged in livestock production. Better management of ASF will be essential to permit the pig sector to reach its full potential as a supplier of high quality protein and a source of income to improve livelihoods and create wealth. No vaccine is currently available and it is likely that, for the near future, the sub-region will continue to rely on the implementation of preventive measures, based on the epidemiology of the disease, to avoid both the devastating losses that outbreaks can cause and the risk the sub-region poses to other parts of Africa and the world. The current situation in the ECSA sub-region is reviewed and gaps in knowledge are identified in order to support ongoing strategy development for managing ASF in endemic areas. This article is protected by copyright. All rights reserved.

Bataille A, Kwiatek O, Belfkhi S, Mounier L, Parida S, Mahapatra M, Caron A, Chubwa C C, Keyyu J, Kock R, Jones B A, Libeau G (2019)

Optimization and evaluation of a non-invasive tool for peste des petits ruminants surveillance and control

Scientific Reports 9 (1), 4742

Abstract

Peste des petits ruminants (PPR) is a highly contagious and devastating viral disease affecting mainly sheep and goats, but also a large number of wild species within the order Artiodactyla. A better understanding of PPR transmission dynamics in multi-host systems is necessary to efficiently control the disease, in particular where wildlife and livestock co-occur. Notably, the role of wildlife in PPR epidemiology is still not clearly understood. Non-invasive strategies to detect PPR infection without the need for animal handling could greatly facilitate research on PPR epidemiology and management of the disease in atypical hosts and in complex field situations. Here, we describe optimized methods for the direct detection of PPR virus genetic material and antigen in fecal samples. We use these methods to determine the detection window of PPR in fecal samples, and compare the sensitivity of these methods to standard invasive sampling and PPR diagnostic methods using field samples collected at a wildlife-livestock interface in Africa. Our results show that quantitative reverse transcription PCR (RT-QPCR) amplification of PPRV from fecal swabs has good sensitivity in comparison to ocular swabs. Animals infected by PPRV could be identified relatively early on and during the whole course of infection based on fecal samples using RT-QPCR. Partial gene sequences could also be retrieved in some cases, from both fecal and ocular samples, providing important information about virus origin and relatedness to other PPRV strains. Non-invasive strategies for PPRV surveillance could provide important data to fill major gaps in our knowledge of the multi-host PPR epidemiology.

Parida S, Selvaraj M, Gubbins S, Pope R, Banyard A, Mahapatra M (2019)

Quantifying levels of peste des petits ruminants (PPR) virus in excretions from experimentally infected goats and its importance for nascent PPR eradication programme

Viruses 11 (3), 249
Publisher’s version: https://doi.org/10.3390/v11030249

Abstract

Following the successful eradication of rinderpest, the World Organization of Animal Health (OIE) and the Food and Agriculture Organisation (FAO) have set a goal to globally eradicate Peste des petits ruminants (PPR) by 2030. To support the eradication programme we have quantified the levels of PPR virus (PPRV) nucleic acid excreted in body fluids (blood, feces, saliva, nasal and eye swabs) of PPRV-infected goats to ascertain which days post-infection animals are potentially infectious, and hence direct quarantine activities. The data will also indicate optimal sample strategies to assess presence of PPR infection in the naturally infected herd. Peak PPRV nucleic acid detection in different bodily fluids was between 5 and 10 days post-infection. As such, this period must be considered the most infectious period for contact transmission, although high viral load was observed through RNA detection in nasal excretions from two days post-infection until at least two weeks post-infection. Percentage sample positivity was low both in eye swabs and saliva samples during the early stage of infection although RNA was detected as late as two weeks post-infection. From the individual animal data, PPRV was detected later post-infection in fecal material than in other body fluids and the detection was intermittent. The results from this study indicate that nasal swabs are the most appropriate to sample when considering molecular diagnosis of PPRV.

Teye M V, Sebunya T K, Fana E M, King D P, Seoke L, Knowles N J, Awuni J A, Matlho G, Leteane M, Hyera J M K (2019)

Foot-and-mouth disease in Southern Ghana: occurrence and molecular characterization of circulating viruses

Tropical Animal Health and Production early view,

Abstract

Foot-and-mouth disease (FMD) is considered to be endemic in Ghana. However, our knowledge of the local epidemiology of the disease is restricted by a lack of serological information and data for characterized viruses causing field outbreaks. In order to improve our understanding of the prevailing situation, this study was initiated to establish the FMD viruses (FMDV) circulating in the country. During 2016, sera (n?=?93) and epithelia/oral swab (n?=?20) samples were collected from cattle from four districts in Southern Ghana that experienced FMD outbreaks. Sera were analyzed using the PrioCHECK® FMDV non-structural protein (NSP) ELISA whereas the epithelia/oral swab samples were examined by virus isolation, antigen ELISA, reverse transcription polymerase chain reaction (RT-PCR), and sequencing of VP1 followed by phylogenetic analysis. Assay for antibodies against FMDV NSPs provided evidence of exposure to FMDV in 88.2% (82/93) of the sera tested. Serotypes O and A viruses were detected from clinical samples by RT-PCR and sequencing of VP1. Phylogenetic analysis of VP1 coding sequences revealed that the serotype O viruses belonged to the West Africa (WA) topotype and were most closely related to viruses from Niger and Benin, while the serotype A viruses clustered within genotype IV (G-IV) of the Africa topotype and were most closely related to viruses from Nigeria. This study provides useful information on FMDV serotypes and viral lineages that circulate in Ghana and West Africa that may aid in the formulation of effective FMD control strategies.

Bondada M S, Yao Y, Nair V (2019)

Multifunctional miR-155 pathway in avian oncogenic virus-induced neoplastic diseases

Non-coding RNA 5 (1), 24

Abstract

MicroRNAs (miRNAs) are small noncoding RNAs that fine-tune the responses of the cell by modulating the cell transcriptome and gene expression. MicroRNA 155 (miR-155) is a conserved multifunctional miRNA involved in multiple roles including the modulation of the immune responses. When deregulated, miR-155 can also contribute to cancer as has been demonstrated in several human malignancies such as diffuse large B cell lymphoma, chronic lymphocytic leukemia, as well as in Epstein(-)Barr virus (EBV)-induced B cell transformation. Avian oncogenic viruses such as Marek's disease virus (MDV), avian leukosis virus (ALV), and reticuloendotheliosis virus (REV) that account for more than 90% of cancers in avian species, also make use of the miR-155 pathway during oncogenesis. While oncogenic retroviruses, such as ALV, activate miR-155 by insertional activation, acutely transforming retroviruses use transduced oncogenes such as v-rel to upregulate miR-155 expression. MDV on the other hand, encodes a functional miR-155 ortholog mdv1-miR-M4, similar to the miR-155 ortholog kshv-miR-K11 present in Kaposi's sarcoma-associated herpesvirus (KSHV). We have shown that mdv1-miR-M4 is critical for the induction of MDV-induced lymphomas further demonstrating the oncogenic potential of miR-155 pathway in cancers irrespective of the diverse etiology. In this review, we discuss on our current understanding of miR-155 function in virus-induced lymphomas focusing primarily on avian oncogenic viruses.

Chanda M M, Carpenter S, Prasad G, Sedda L, Henrys P A, Gajendragad M R, Purse B V (2019)

Livestock host composition rather than land use or climate explains spatial patterns in bluetongue disease in South India

Scientific Reports 9 (1), 4229

Abstract

Culicoides-borne arboviruses of livestock impair animal health, livestock production and livelihoods worldwide. As these arboviruses are multi-host, multi-vector systems, predictions to improve targeting of disease control measures require frameworks that quantify the relative impacts of multiple abiotic and biotic factors on disease patterns. We develop such a framework to predict long term (1992-2009) average patterns in bluetongue (BT), caused by bluetongue virus (BTV), in sheep in southern India, where annual BT outbreaks constrain the livelihoods and production of small-holder farmers. In Bayesian spatial general linear mixed models, host factors outperformed landscape and climate factors as predictors of disease patterns, with more BT outbreaks occurring on average in districts with higher densities of susceptible sheep breeds and buffalo. Since buffalo are resistant to clinical signs of BT, this finding suggests they are a source of infection for sympatric susceptible sheep populations. Sero-monitoring is required to understand the role of buffalo in maintaining BTV transmission and whether they must be included in vaccination programs to protect sheep adequately. Landscape factors, namely the coverage of post-flooding, irrigated and rain-fed croplands, had weak positive effects on outbreaks. The intimate links between livestock host, vector composition and agricultural practices in India require further investigation at the landscape scale.

Dixon L K, Sun H, Roberts H (2019)

African swine fever

Antiviral Research 165, 34-41

Abstract

The continuing spread of African swine fever (ASF) outside Africa in Europe, the Russian Federation, China and most recently to Mongolia and Vietnam, has heightened awareness of the threat posed by this devastating disease to the global pig industry and food security. In this review we summarise what we know about the African swine fever virus (ASFV), the disease it causes, how it spreads and the current global situation. We discuss current control methods in domestic and wild pigs and prospects for development of vaccines and other tools for control.

Pang Y, Zhou D, Xue J, Zhou J, Zhang Y, Zheng G, Yuan S, Yao Y, Cheng Z (2019)

Interplay between CTHRC1 and the SU protein of avian leukosis virus subgroup J (ALV-J) facilitates viral replication

Virus Research 264, 32-39

Abstract

The lifecycle of avian leukosis virus subgroup J (ALV-J), a typical tumorigenic retrovirus, is highly dependent upon host cellular proteins. However, there have been few studies directed at uncovering the host proteins responsible for ALV-J replication, which could provide insights into new strategies for ALV-J prevention and control. Here, we used proteomics to identify the association of differential levels of collagen triple helix-repeat-containing 1 (CTHRC1) and with viral replication. Our results revealed that CTHRC1 was significantly upregulated in ALV-J-infected cells in vitro, and these findings were confirmed in vivo. Additionally, CTHRC1 overexpression facilitated ALV-J replication, whereas CTHRC1 knockdown suppressed this activity. Moreover, we found that ALV-J drove CTHRC1 translocation from the nucleus to the cytosol through interactions with the ALV-J envelope glycoprotein. These results revealed CTHRC1 as a shutting protein recruited by ALV-J to facilitate viral replication.

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